Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy - a clinical and neurophysiological study.
The efficacy of treatment with an aldose reductase inhibitor (1,3-dioxo-1 H-benz-de-isoquinoline-2(3H)-acetic acid, AY-22,284, Alrestatin) on peripheral nerve function in diabetic polyneuropathy was assessed. Thirty patients with long-standing diabetes and slight to moderate neuropathy participated in the double-blind placebo trial. Clinical examination, sensory threshold determinations for vibratory, tactile and thermal stimuli, conduction velocity measurements and studies of automatic function were performed to evaluate the treatment. Significant differences favouring Alrestatin over placebo were found for many of the measured variables, whereas no changes occurred on placebo. The apparent improvement of neuropathy occurred despite persisting hyperglycaemia. The results indicate that aldose reductase inhibitor treatment may be of value in diabetic polyneuropathy, and provide support for the sorbitol pathway hypothesis of diabetic polyneuropathy.
D000328:Adult; D000419:Albuminuria / Q000139:chemically induced; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001341:Autonomic Nervous System / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012677:Sensation / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007546:Isoquinolines; D013012:Sorbitol; C016212:alrestatin; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase